13-36077718-G-C

Variant names:

• chr13-36077718-G-C
• rs9315383
• NM_001330071.2:c.723+34151C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.723+34151C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,054 control chromosomes in the GnomAD database, including 26,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26986 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 3 publications found

Genes affected

DCLK1 (HGNC:2700): (doublecortin like kinase 1) This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.723+34151C>G		intron_variant	Intron 3 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.723+34151C>G		intron_variant	Intron 3 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.723+34151C>G		intron_variant	Intron 3 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.723+34151C>G		intron_variant	Intron 3 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89788 AN: 151934 Hom.: 26955 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.591 AC: 89861 AN: 152054 Hom.: 26986 Cov.: 32 AF XY: 0.593 AC XY: 44040 AN XY: 74326

African (AFR) AF: 0.651 AC: 27013 AN: 41488

American (AMR) AF: 0.613 AC: 9362 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4470 AN: 5172

South Asian (SAS) AF: 0.705 AC: 3401 AN: 4824

European-Finnish (FIN) AF: 0.476 AC: 5022 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36628 AN: 67954

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.562 Hom.: 3018

Bravo AF: 0.604

Asia WGS AF: 0.789 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.32
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9315383; hg19: chr13-36651855;